Incidental Mutation 'R7153:Npc1'
| ID |
554293 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Npc1
|
| Ensembl Gene |
ENSMUSG00000024413 |
| Gene Name |
NPC intracellular cholesterol transporter 1 |
| Synonyms |
lcsd, nmf164, D18Ertd139e, D18Ertd723e, A430089E03Rik, C85354 |
| MMRRC Submission |
045255-MU
|
| Accession Numbers |
|
| Essential gene? |
Possibly essential
(E-score: 0.616)
|
| Stock # |
R7153 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Validated
|
| Chromosome |
18 |
| Chromosomal Location |
12322749-12369457 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to G
at 12346348 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Phenylalanine to Leucine
at position 283
(F283L)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000025279
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000025279]
|
| AlphaFold |
O35604 |
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000025279
AA Change: F283L
PolyPhen 2
Score 0.776 (Sensitivity: 0.85; Specificity: 0.92)
|
| SMART Domains |
Protein: ENSMUSP00000025279
Gene: ENSMUSG00000024413
AA Change: F283L
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
8 |
15 |
N/A |
INTRINSIC |
|
Pfam:NPC1_N
|
22 |
267 |
1.6e-79 |
PFAM |
|
transmembrane domain
|
269 |
291 |
N/A |
INTRINSIC |
|
transmembrane domain
|
353 |
375 |
N/A |
INTRINSIC |
|
Pfam:Patched
|
436 |
896 |
3.5e-52 |
PFAM |
|
Pfam:MMPL
|
648 |
794 |
6.3e-8 |
PFAM |
|
Pfam:Sterol-sensing
|
649 |
803 |
2.7e-56 |
PFAM |
|
Pfam:Patched
|
1023 |
1252 |
2.9e-33 |
PFAM |
|
low complexity region
|
1259 |
1273 |
N/A |
INTRINSIC |
|
| Meta Mutation Damage Score |
0.3881 |
| Coding Region Coverage |
- 1x: 100.0%
- 3x: 99.9%
- 10x: 99.6%
- 20x: 98.8%
|
| Validation Efficiency |
100% (75/75) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a large protein that resides in the limiting membrane of endosomes and lysosomes and mediates intracellular cholesterol trafficking via binding of cholesterol to its N-terminal domain. It is predicted to have a cytoplasmic C-terminus, 13 transmembrane domains, and 3 large loops in the lumen of the endosome - the last loop being at the N-terminus. This protein transports low-density lipoproteins to late endosomal/lysosomal compartments where they are hydrolized and released as free cholesterol. Defects in this gene cause Niemann-Pick type C disease, a rare autosomal recessive neurodegenerative disorder characterized by over accumulation of cholesterol and glycosphingolipids in late endosomal/lysosomal compartments.[provided by RefSeq, Aug 2009]
PHENOTYPE: Homozygotes for spontaneous and chemically induced mutations may exhibit lysosomal storage of non-esterified cholesterol, neurodegeneration, ataxia, presence of foam cells, sterility, and shortened lifespan. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 75 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Ano2 |
A |
G |
6: 125,969,906 (GRCm39) |
T741A |
possibly damaging |
Het |
| Aox4 |
T |
C |
1: 58,289,378 (GRCm39) |
M767T |
probably damaging |
Het |
| Arhgap39 |
C |
A |
15: 76,649,691 (GRCm39) |
S27I |
probably benign |
Het |
| AU018091 |
T |
A |
7: 3,209,353 (GRCm39) |
M296L |
probably benign |
Het |
| Axin1 |
A |
G |
17: 26,406,942 (GRCm39) |
T512A |
probably benign |
Het |
| B4galnt3 |
A |
T |
6: 120,191,929 (GRCm39) |
D602E |
probably benign |
Het |
| Bcl6 |
G |
A |
16: 23,784,976 (GRCm39) |
R675* |
probably null |
Het |
| Bsnd |
A |
T |
4: 106,349,230 (GRCm39) |
D3E |
probably benign |
Het |
| Btbd18 |
C |
T |
2: 84,496,772 (GRCm39) |
R137* |
probably null |
Het |
| C2cd5 |
A |
G |
6: 142,965,135 (GRCm39) |
S871P |
probably benign |
Het |
| Cobl |
G |
T |
11: 12,204,128 (GRCm39) |
P858Q |
probably damaging |
Het |
| Col6a1 |
C |
T |
10: 76,546,175 (GRCm39) |
|
probably null |
Het |
| Crb2 |
A |
T |
2: 37,677,420 (GRCm39) |
H304L |
probably benign |
Het |
| Crybg1 |
T |
A |
10: 43,840,662 (GRCm39) |
Y1812F |
possibly damaging |
Het |
| Ddx60 |
A |
T |
8: 62,441,142 (GRCm39) |
K1070N |
possibly damaging |
Het |
| Defb22 |
T |
C |
2: 152,327,840 (GRCm39) |
K115R |
unknown |
Het |
| Dhx8 |
C |
T |
11: 101,631,001 (GRCm39) |
|
probably null |
Het |
| Dnah5 |
T |
A |
15: 28,365,668 (GRCm39) |
|
probably null |
Het |
| Dnah7b |
T |
A |
1: 46,165,964 (GRCm39) |
F543Y |
probably benign |
Het |
| Ehhadh |
A |
G |
16: 21,585,071 (GRCm39) |
F270S |
probably damaging |
Het |
| Esyt2 |
A |
G |
12: 116,310,128 (GRCm39) |
M397V |
probably benign |
Het |
| Fanca |
A |
T |
8: 124,043,164 (GRCm39) |
L74H |
probably damaging |
Het |
| Fbxl17 |
C |
A |
17: 63,367,346 (GRCm39) |
V676F |
probably benign |
Het |
| Fndc1 |
A |
G |
17: 8,020,477 (GRCm39) |
V102A |
probably damaging |
Het |
| Gpalpp1 |
T |
C |
14: 76,332,451 (GRCm39) |
Y273C |
probably damaging |
Het |
| Gpatch8 |
TTCCTCCTCCTCCTCTTCCTCCTCCTC |
TTCCTCCTCCTCCTCCTCTTCCTCCTCCTC |
11: 102,371,014 (GRCm39) |
|
probably benign |
Het |
| Grik2 |
T |
C |
10: 49,411,463 (GRCm39) |
H225R |
probably benign |
Het |
| Helz2 |
A |
T |
2: 180,873,078 (GRCm39) |
S2411T |
probably benign |
Het |
| Hnmt |
C |
T |
2: 23,904,353 (GRCm39) |
A103T |
probably damaging |
Het |
| Ighv15-2 |
G |
T |
12: 114,528,210 (GRCm39) |
Y114* |
probably null |
Het |
| Irak2 |
A |
G |
6: 113,655,670 (GRCm39) |
H357R |
probably benign |
Het |
| Kcp |
T |
C |
6: 29,499,014 (GRCm39) |
E320G |
probably damaging |
Het |
| Kpna4 |
A |
G |
3: 68,997,131 (GRCm39) |
L352S |
probably damaging |
Het |
| Krt36 |
G |
A |
11: 99,995,972 (GRCm39) |
Q151* |
probably null |
Het |
| Krt77 |
G |
A |
15: 101,773,931 (GRCm39) |
T241M |
probably benign |
Het |
| Lca5l |
T |
A |
16: 95,975,009 (GRCm39) |
N305I |
probably damaging |
Het |
| Lefty1 |
T |
A |
1: 180,765,332 (GRCm39) |
L300Q |
probably benign |
Het |
| Mertk |
A |
G |
2: 128,578,569 (GRCm39) |
Y185C |
probably damaging |
Het |
| Mmp14 |
T |
C |
14: 54,673,708 (GRCm39) |
I124T |
possibly damaging |
Het |
| Nlrc4 |
T |
C |
17: 74,754,098 (GRCm39) |
E95G |
possibly damaging |
Het |
| Or4k38 |
A |
T |
2: 111,166,246 (GRCm39) |
M59K |
probably damaging |
Het |
| Or4p19 |
A |
C |
2: 88,242,462 (GRCm39) |
L180W |
probably damaging |
Het |
| Pcdha11 |
T |
C |
18: 37,144,278 (GRCm39) |
V123A |
probably damaging |
Het |
| Pcdhga2 |
T |
C |
18: 37,802,261 (GRCm39) |
V35A |
probably damaging |
Het |
| Pgd |
G |
T |
4: 149,246,135 (GRCm39) |
T94K |
probably benign |
Het |
| Pik3c2a |
T |
C |
7: 115,941,487 (GRCm39) |
N1593S |
probably damaging |
Het |
| Pkd1l3 |
GACACCTGCATCCAGCAGCCCAACAAACATGACATCAGACACACCTGCATCCAGCAGCCCAACAAACATGACATCAGACACACCTGCATCCAGCAGCCCAACAAACATGACATCAGACACACCTGCATCCAGCAGCCCA |
GACACCTGCATCCAGCAGCCCAACAAACATGACATCAGACACACCTGCATCCAGCAGCCCAACAAACATGACATCAGACACACCTGCATCCAGCAGCCCA |
8: 110,350,827 (GRCm39) |
|
probably benign |
Het |
| Plcb3 |
A |
G |
19: 6,935,452 (GRCm39) |
|
probably null |
Het |
| Prkd3 |
C |
T |
17: 79,273,784 (GRCm39) |
D491N |
probably benign |
Het |
| Ptprf |
T |
C |
4: 118,088,740 (GRCm39) |
T688A |
probably damaging |
Het |
| Pycr2 |
T |
A |
1: 180,734,247 (GRCm39) |
L210M |
probably damaging |
Het |
| Rpl36 |
T |
C |
17: 56,921,137 (GRCm39) |
I81T |
probably benign |
Het |
| Rraga |
C |
T |
4: 86,494,253 (GRCm39) |
A33V |
probably damaging |
Het |
| Slc29a1 |
G |
A |
17: 45,896,688 (GRCm39) |
A429V |
probably damaging |
Het |
| Stab1 |
T |
G |
14: 30,882,541 (GRCm39) |
E432A |
probably benign |
Het |
| Synj1 |
C |
T |
16: 90,744,978 (GRCm39) |
G1189R |
probably benign |
Het |
| Synpo2 |
A |
G |
3: 122,906,053 (GRCm39) |
*1088Q |
probably null |
Het |
| Tbc1d21 |
T |
C |
9: 58,270,376 (GRCm39) |
D133G |
probably damaging |
Het |
| Tenm2 |
A |
G |
11: 35,915,009 (GRCm39) |
V2176A |
probably damaging |
Het |
| Tff1 |
A |
G |
17: 31,381,772 (GRCm39) |
I35T |
probably benign |
Het |
| Thnsl1 |
T |
C |
2: 21,217,764 (GRCm39) |
V506A |
possibly damaging |
Het |
| Timm10b |
A |
G |
7: 105,290,087 (GRCm39) |
Q50R |
unknown |
Het |
| Tjp2 |
A |
T |
19: 24,079,345 (GRCm39) |
N843K |
probably benign |
Het |
| Tle1 |
A |
T |
4: 72,057,298 (GRCm39) |
F101I |
probably benign |
Het |
| Tmem225 |
T |
C |
9: 40,059,664 (GRCm39) |
F15L |
probably benign |
Het |
| Trav12-3 |
T |
C |
14: 53,859,618 (GRCm39) |
L88P |
probably benign |
Het |
| Ttc7b |
A |
T |
12: 100,321,293 (GRCm39) |
W613R |
probably damaging |
Het |
| Ttn |
T |
A |
2: 76,608,848 (GRCm39) |
M17723L |
probably benign |
Het |
| Ttn |
T |
C |
2: 76,775,660 (GRCm39) |
D1840G |
unknown |
Het |
| Tubgcp2 |
T |
C |
7: 139,580,949 (GRCm39) |
H668R |
probably benign |
Het |
| Ush2a |
C |
A |
1: 188,460,681 (GRCm39) |
N2647K |
possibly damaging |
Het |
| Vmn1r14 |
C |
T |
6: 57,210,851 (GRCm39) |
S143F |
probably benign |
Het |
| Vmn2r70 |
A |
G |
7: 85,214,262 (GRCm39) |
S297P |
probably damaging |
Het |
| Ywhab |
T |
C |
2: 163,855,980 (GRCm39) |
F119L |
probably damaging |
Het |
| Zmym2 |
T |
A |
14: 57,187,659 (GRCm39) |
D1108E |
probably benign |
Het |
|
| Other mutations in Npc1 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL02347:Npc1
|
APN |
18 |
12,332,691 (GRCm39) |
missense |
probably benign |
0.45 |
|
IGL02523:Npc1
|
APN |
18 |
12,334,629 (GRCm39) |
missense |
probably benign |
0.00 |
|
IGL03018:Npc1
|
APN |
18 |
12,347,436 (GRCm39) |
missense |
probably damaging |
0.99 |
|
IGL03101:Npc1
|
APN |
18 |
12,331,596 (GRCm39) |
missense |
probably benign |
0.15 |
|
IGL03151:Npc1
|
APN |
18 |
12,352,332 (GRCm39) |
missense |
probably benign |
0.05 |
|
IGL03377:Npc1
|
APN |
18 |
12,344,878 (GRCm39) |
missense |
probably benign |
|
|
PIT4354001:Npc1
|
UTSW |
18 |
12,344,592 (GRCm39) |
missense |
probably benign |
0.00 |
|
R0068:Npc1
|
UTSW |
18 |
12,341,424 (GRCm39) |
missense |
probably benign |
0.04 |
|
R0068:Npc1
|
UTSW |
18 |
12,341,424 (GRCm39) |
missense |
probably benign |
0.04 |
|
R0190:Npc1
|
UTSW |
18 |
12,324,887 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0200:Npc1
|
UTSW |
18 |
12,352,261 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0485:Npc1
|
UTSW |
18 |
12,346,503 (GRCm39) |
missense |
probably benign |
0.00 |
|
R0699:Npc1
|
UTSW |
18 |
12,343,632 (GRCm39) |
missense |
probably benign |
0.00 |
|
R0730:Npc1
|
UTSW |
18 |
12,352,382 (GRCm39) |
missense |
probably benign |
0.00 |
|
R1302:Npc1
|
UTSW |
18 |
12,328,142 (GRCm39) |
missense |
probably benign |
0.00 |
|
R1442:Npc1
|
UTSW |
18 |
12,328,106 (GRCm39) |
missense |
probably benign |
|
|
R1463:Npc1
|
UTSW |
18 |
12,324,887 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1804:Npc1
|
UTSW |
18 |
12,356,145 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1808:Npc1
|
UTSW |
18 |
12,327,149 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1928:Npc1
|
UTSW |
18 |
12,346,435 (GRCm39) |
missense |
possibly damaging |
0.79 |
|
R2112:Npc1
|
UTSW |
18 |
12,346,529 (GRCm39) |
missense |
possibly damaging |
0.49 |
|
R2117:Npc1
|
UTSW |
18 |
12,329,613 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2157:Npc1
|
UTSW |
18 |
12,324,866 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R2279:Npc1
|
UTSW |
18 |
12,330,236 (GRCm39) |
splice site |
probably null |
|
|
R2311:Npc1
|
UTSW |
18 |
12,335,240 (GRCm39) |
missense |
probably benign |
|
|
R2446:Npc1
|
UTSW |
18 |
12,347,396 (GRCm39) |
missense |
probably benign |
0.01 |
|
R3004:Npc1
|
UTSW |
18 |
12,330,311 (GRCm39) |
missense |
probably benign |
0.03 |
|
R4090:Npc1
|
UTSW |
18 |
12,331,219 (GRCm39) |
splice site |
probably null |
|
|
R4304:Npc1
|
UTSW |
18 |
12,343,584 (GRCm39) |
missense |
possibly damaging |
0.77 |
|
R4308:Npc1
|
UTSW |
18 |
12,343,584 (GRCm39) |
missense |
possibly damaging |
0.77 |
|
R4564:Npc1
|
UTSW |
18 |
12,324,789 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4786:Npc1
|
UTSW |
18 |
12,332,554 (GRCm39) |
missense |
probably benign |
0.35 |
|
R5243:Npc1
|
UTSW |
18 |
12,331,688 (GRCm39) |
intron |
probably benign |
|
|
R5404:Npc1
|
UTSW |
18 |
12,346,356 (GRCm39) |
missense |
possibly damaging |
0.79 |
|
R5823:Npc1
|
UTSW |
18 |
12,324,846 (GRCm39) |
missense |
possibly damaging |
0.69 |
|
R6080:Npc1
|
UTSW |
18 |
12,352,408 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6215:Npc1
|
UTSW |
18 |
12,369,249 (GRCm39) |
small deletion |
probably benign |
|
|
R6301:Npc1
|
UTSW |
18 |
12,330,302 (GRCm39) |
missense |
probably benign |
0.00 |
|
R6476:Npc1
|
UTSW |
18 |
12,334,751 (GRCm39) |
nonsense |
probably null |
|
|
R7007:Npc1
|
UTSW |
18 |
12,343,605 (GRCm39) |
missense |
probably benign |
0.02 |
|
R7020:Npc1
|
UTSW |
18 |
12,331,594 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7048:Npc1
|
UTSW |
18 |
12,337,822 (GRCm39) |
splice site |
probably null |
|
|
R7116:Npc1
|
UTSW |
18 |
12,344,601 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7359:Npc1
|
UTSW |
18 |
12,328,237 (GRCm39) |
missense |
probably benign |
0.05 |
|
R7382:Npc1
|
UTSW |
18 |
12,334,763 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R7765:Npc1
|
UTSW |
18 |
12,328,105 (GRCm39) |
missense |
probably benign |
0.01 |
|
R8047:Npc1
|
UTSW |
18 |
12,346,374 (GRCm39) |
missense |
probably benign |
0.00 |
|
R8094:Npc1
|
UTSW |
18 |
12,327,297 (GRCm39) |
missense |
probably benign |
|
|
R8161:Npc1
|
UTSW |
18 |
12,328,129 (GRCm39) |
missense |
possibly damaging |
0.77 |
|
R8310:Npc1
|
UTSW |
18 |
12,326,455 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R8821:Npc1
|
UTSW |
18 |
12,333,877 (GRCm39) |
missense |
probably benign |
0.01 |
|
R8831:Npc1
|
UTSW |
18 |
12,333,877 (GRCm39) |
missense |
probably benign |
0.01 |
|
R8847:Npc1
|
UTSW |
18 |
12,323,987 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9022:Npc1
|
UTSW |
18 |
12,346,422 (GRCm39) |
missense |
probably benign |
|
|
R9343:Npc1
|
UTSW |
18 |
12,334,769 (GRCm39) |
missense |
possibly damaging |
0.52 |
|
R9460:Npc1
|
UTSW |
18 |
12,346,398 (GRCm39) |
missense |
possibly damaging |
0.93 |
|
R9723:Npc1
|
UTSW |
18 |
12,343,649 (GRCm39) |
missense |
probably benign |
|
|
X0012:Npc1
|
UTSW |
18 |
12,326,368 (GRCm39) |
splice site |
probably null |
|
|
| Predicted Primers |
PCR Primer
(F):5'- TTACTAGCTGTAGGCACAAGC -3'
(R):5'- AGATCTTTCAATCCTTGGGATGG -3'
Sequencing Primer
(F):5'- GCACAAGCCATCCAGGG -3'
(R):5'- TCAATCCTTGGGATGGAGCCC -3'
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| Posted On |
2019-05-15 |
Incidental Mutation